Geographical disparities in core population coverage indicators for roll back malaria in Malawi

BACKGROUND: Implementation of known effective interventions would necessitate the reduction of malaria burden by half by the year 2010. Identifying geographical disparities of coverage of these interventions at small area level is useful to inform where greatest scaling-up efforts should be concentrated. They also provide baseline data against which future scaling-up of interventions can be compared. However, population data are not always available at local level. This study applied spatial smoothing methods to generate maps at subdistrict level in Malawi to serve such purposes. METHODS: Data for the following responses from the 2000 Malawi Demographic and Health Survey (DHS) were aggregated at subdistrict level: (1) households possessing at least one bednet; (2) children under 5 years who slept under a bednet the night before the survey; (3) bednets retreated with insecticide within past 6-12 months preceding the survey; (4) children under 5 who had fever two weeks before the survey and received treatment within 24 hours from the onset of fever; and (5) women who received intermittent preventive treatment of malaria during their last pregnancy. Each response was geographically smoothed at subdistrict level by applying conditional autoregressive models using Markov Chain Monte Carlo simulation techniques. RESULTS: The underlying geographical patterns of coverage of indicators were more clear in the smoothed maps than in the original unsmoothed maps, with relatively high coverage in urban areas than in rural areas for all indicators. The percentage of households possessing at least one bednet was 19% (95% credible interval (CI): 16-21%), with 9% (95% CI: 7-11%) of children sleeping under a net, while 18% (95% CI: 16-19%) of households had retreated their nets within past 12 months prior to the survey. The northern region and lakeshore areas had high bednet coverage, but low usage and re-treatment rates. Coverage rate of children who received antimalarial treatment within 24 hours after onset of fever was consistently low for most parts of the country, with mean coverage of 4.8% (95% CI: 4.5-5.0%). About 48% (95% CI: 47-50%) of women received antimalarial prophylaxis during their pregnancy, with highest rates in the southern and northern areas. CONCLUSION: The striking geographical patterns, for example between predominantly urban and rural areas, may reflect spatial differences in provider compliance or coverage, and can partly be explained by socio-economic and cultural differences. The wide gap between high bed net coverage and low retreatment rates may reflect variation in perceptions about malaria, which may be addressed by implementing information, education and communication campaigns or introducing long lasting insecticide nets. Our results demonstrate that DHS data, with appropriate methodology, can provide acceptable estimates at sub-national level for monitoring and evaluation of malaria control goals

A time projection chamber for high accuracy and precision fission cross-section measurements

The fission Time Projection Chamber (fissionTPC) is a compact (15 cm diameter) two-chamber MICROMEGAS TPC designed to make precision cross-section measurements of neutron-induced fission. The actinide targets are placed on the central cathode and irradiated with a neutron beam that passes axially through the TPC inducing fission in the target. The 4π acceptance for fission fragments and complete charged particle track reconstruction are powerful features of the fissionTPC which will be used to measure fission cross-sections and examine the associated systematic errors. This paper provides a detailed description of the design requirements, the design solutions, and the initial performance of the fissionTPC.Keywords: Detectors, Fission, Time Projection Chamber, TP

Enhancer redundancy provides phenotypic robustness in mammalian development.

Distant-acting tissue-specific enhancers, which regulate gene expression, vastly outnumber protein-coding genes in mammalian genomes, but the functional importance of this regulatory complexity remains unclear. Here we show that the pervasive presence of multiple enhancers with similar activities near the same gene confers phenotypic robustness to loss-of-function mutations in individual enhancers. We used genome editing to create 23 mouse deletion lines and inter-crosses, including both single and combinatorial enhancer deletions at seven distinct loci required for limb development. Unexpectedly, none of the ten deletions of individual enhancers caused noticeable changes in limb morphology. By contrast, the removal of pairs of limb enhancers near the same gene resulted in discernible phenotypes, indicating that enhancers function redundantly in establishing normal morphology. In a genetic background sensitized by reduced baseline expression of the target gene, even single enhancer deletions caused limb abnormalities, suggesting that functional redundancy is conferred by additive effects of enhancers on gene expression levels. A genome-wide analysis integrating epigenomic and transcriptomic data from 29 developmental mouse tissues revealed that mammalian genes are very commonly associated with multiple enhancers that have similar spatiotemporal activity. Systematic exploration of three representative developmental structures (limb, brain and heart) uncovered more than one thousand cases in which five or more enhancers with redundant activity patterns were found near the same gene. Together, our data indicate that enhancer redundancy is a remarkably widespread feature of mammalian genomes that provides an effective regulatory buffer to prevent deleterious phenotypic consequences upon the loss of individual enhancers

Enhancer redundancy provides phenotypic robustness in mammalian development.

Distant-acting tissue-specific enhancers, which regulate gene expression, vastly outnumber protein-coding genes in mammalian genomes, but the functional importance of this regulatory complexity remains unclear. Here we show that the pervasive presence of multiple enhancers with similar activities near the same gene confers phenotypic robustness to loss-of-function mutations in individual enhancers. We used genome editing to create 23 mouse deletion lines and inter-crosses, including both single and combinatorial enhancer deletions at seven distinct loci required for limb development. Unexpectedly, none of the ten deletions of individual enhancers caused noticeable changes in limb morphology. By contrast, the removal of pairs of limb enhancers near the same gene resulted in discernible phenotypes, indicating that enhancers function redundantly in establishing normal morphology. In a genetic background sensitized by reduced baseline expression of the target gene, even single enhancer deletions caused limb abnormalities, suggesting that functional redundancy is conferred by additive effects of enhancers on gene expression levels. A genome-wide analysis integrating epigenomic and transcriptomic data from 29 developmental mouse tissues revealed that mammalian genes are very commonly associated with multiple enhancers that have similar spatiotemporal activity. Systematic exploration of three representative developmental structures (limb, brain and heart) uncovered more than one thousand cases in which five or more enhancers with redundant activity patterns were found near the same gene. Together, our data indicate that enhancer redundancy is a remarkably widespread feature of mammalian genomes that provides an effective regulatory buffer to prevent deleterious phenotypic consequences upon the loss of individual enhancers